Look-ahead policies for admission to a single server loss system

Consider a single server loss system in which the server, being idle, may reject or accept an arriving customer for service depending on the state at the arrival epoch. It is assumed that at every arrival epoch the server knows the service time of the arriving customer, the arrival time of the next customer and the service time. The server gets a fixed reward for every customer admitted to the system. The form of an optimal stationary policy is investigated for the discounted and average reward cases

On a random interval graph and the maximum throughput rate in the system GI/G/1/0

The paper gives an explicit expression for the expectation of the maximum attainable fraction of served customers in the long run for the single-server loss system GI/GI1/0, under the assumption of perfect information regarding the sequences {X,, i = 1, 2, - - - } and {Yi, i = 1, 2, ..--- } of interarrival times and service times, respectively. A heavy traffic result for this fraction is obtained for the system GI/M/1/0. The general result is based on an analysis of the random interval graph corresponding to the random intervals {[Ti, T1 + Y), i = 1,2,... }, in which { I} denotes the sequence of arrival epochs

The effect of crack length and maximum stress on the fatigue crack growth rates of engineering alloys

The fatigue crack growth rate (FCGR) curve of metallic alloys is usually divided into three regions. Region II is often referred to as the Paris regime and is usually modelled with a power law relationship with a single exponent. Regions I and III are located at the beginning and end of the FCGR curve, respectively, and are frequently modelled with asymptotic relationships. In this paper we hypothesize that fatigue crack growth is governed by power law behaviour at all crack lengths and all stress intensity factor ranges (ΔK). To accommodate for the changes in the FCGR slope at regions I - III mathematical pivot points are introduced in the Paris equation. Power law behaviour with the presence of pivot points enables direct fitting of the crack length vs. cycles (a-N) curve to obtain the FCGR as a function of ΔK. This novel approach is applicable to small and long crack growth curves and results in accurate multilinear FCGR curves that are suitable for reconstruction of the measured a-N curves. The method is subsequently applied to i) different alloys to show local changes in the FCGR curve for changes in alloy composition and heat treatments, ii) naturally increasing ΔK testing of microstructurally small cracks to obtain accurate small crack FCGR data. The comparison with accurate long crack data shows that small cracks are faster, but the transition from region I to region II occurs at a specific fatigue crack growth rate which results in an apparent shift in ΔK at the transition. iii) Long cracks, which show that the FCGR increases with maximum stress for a given ΔK and stress ratio when the maximum stress approaches the yield stress. The maximum stress phenomenon becomes important in the case of fatigue testing, where the initial crack lengths are usually small and maximum stresses are high. It is concluded that for long cracks the phenomenon explains why the Paris equation is applicable rather at low maximum stress, while the Frost-Dugdale equation is more applicable at high maximum stress

The central role of IL-33/IL-1RL1 pathway in asthma:From pathogenesis to intervention

Interleukin-33 (IL-33), a member of the IL-1 family, and its cognate receptor, Interleukin-1 receptor like-1 (IL-1RL1 or ST2), are susceptibility genes for childhood asthma. In response to cellular damage, IL-33 is released from barrier tissues as an & lsquo;alarmin & rsquo; to activate the innate immune response. IL-33 drives type 2 responses by inducing signalling through its receptor IL-1RL1 in several immune and structural cells, thereby leading to type 2 cytokine and chemokine production. IL-1RL1 gene transcript encodes different isoforms generated through alternative splicing. Its soluble isoform, IL-1RL1-a or sST2, acts as a decoy receptor by sequestering IL-33, thereby inhibiting IL1RL1-b/IL-33 signalling. IL-33 and its receptor IL-1RL1 are therefore considered as putative biomarkers or targets for pharmacological intervention in asthma. This review will provide an overview of the genetics and biology of the IL-33/IL-1RL1 pathway in the context of asthma pathogenesis. It will discuss the potential and complexities of targeting the cytokine or its receptor, how genetics or biomarkers may inform precision medicine for asthma targeting this pathway, and the possible positioning of therapeutics targeting IL-33 or its receptor in the expanding landscape of novel biologicals applied in asthma management. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

IL-1RL1a serum levels and IL1RL1 SNPs in the prediction of food allergy

Food allergy is a common disorder in the Western world, with increasing prevalence and substantial healthcare costs(1). Food allergy is often accompanied by the presence of specific IgE against harmless proteins in food, but not all sensitized children show clinical reactions upon exposure. Therefore, double-blind placebo-controlled food challenges (DBPCFC) remain the gold standard to diagnose food allergy, yet this test is demanding. Biomarkers that can predict clinical response to food are urgently needed

Allergen immunotherapy for allergic airway diseases:Use lessons from the past to design a brighter future

Allergic respiratory diseases, such as allergic dermatitis, food allergy, allergic rhino conjunctivitis and allergic asthma, are chronic inflammatory diseases with increasing prevalence. Symptoms include such as watery or itchy itching of the mouth, skin, or the eyes, swelling of the face or throat, sneezing, congestion or vomiting, wheezing, shortness of breath and coughing. For allergic asthma, additional symptoms include tightness of chest, cough, wheezing, and reversible airflow limitation. These symptoms can be triggered by inhalation of aller -gens such as food allergens or airborne allergens such as those from tree-or grass pollen and house dust mites. Pharmacological intervention in allergic disease includes the use of antihistamines, immune suppressive drugs and in case of asthma, the use of (long acting) beta-agonists for relaxation of the constricted airways. These treat-ment options merely suppress symptoms and do not cure the disease. Allergen immunotherapy (AIT), in con -trast, has the capacity of inducing long-term tolerance, with symptom relief persisting decennia after discontinuation of treatment, despite recurrent re-exposure to the allergen. However, AIT is not effective for all allergic disorders, and treatment for several years is required to obtain long-term protection. Moreover, some forms of AIT have safety concerns, with risk of mild to severe allergic reactions. To improve safety and efficacy of AIT, the underlying mechanisms have been studied extensively in the clinic as well as in experimental models of allergic airway inflammation.Despite more than a century of clinical experience and a vast body of experimental and translational studies into the immunological and cellular mechanisms underpinning its therapeutic potential, AIT is still not implemented in routine clinical care for allergic asthma. This review provides an overview of the substantial developments that contribute to our knowledge of the pathogenesis of allergic airway diseases, the mechanism of action of AIT, its treatment routes and schedules, the standardization of extracts and use of adjuvantia. Moreover, the main con-clusions from experimental models of AIT with regard to the safety and effectiveness of the treatment are summarized, and future directions for further improvements are outlined. AIT urgently requires further improvements in order to increase its efficiency and shorten the treatment duration while remaining safe and costeffective.(c) 2022 Published by Elsevier Inc

1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT